Preparation of 3, 3', 5, 5'-tetrakis(1-methyl)biphenyl-4,4'-diol ( 4) Propofol (1) (5 g, 28 mmol) was charged into water (150 mL) followed by addition of FeCl 3 (5.6 g, 30.3 mmol) and the reaction mixture was heated at 90 o C for 1 h. Reaction mixture was allowed to cool to room temperature and extracted with ethyl acetate (2 × 75 mL). Combined organic layer was dried over sodium sulphate, filtered and concentrated to give the crude product which was used as such for the next step. To a solution of crude residue in THF (45 mL) and MeOH (5 mL), was added sodium borohydride (3.2 g, 84 mmol) and reaction mixture was stirred

An efficient, short manufacturing process for fenspiride hydrochloride is reported. Nitro-aldol condensation is the key reaction in the developed process. Improved routes to key building blocks are demonstrated by expedient multikilogram production. Hazardous reactions are avoided. API produced following this new route meets the quality requirement NLT 99.70% purity by HPLC with any individual impurity NMT 0.10% with very good yield.

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